Drug delivery compositions and methods
The present invention provides compositions and methods for the delivery of therapeutics to a cell or subject.
1. A micelle comprising
a) at least one block copolymer comprising an ionically charged polymeric segment and a non-ionically charged polymeric segment, wherein said ionically charged polymeric segment is grafted with hydrophobic moieties as side chains of said ionically charged polymeric segment, wherein said ionically charged polymeric segment is cross-linked and forms the core of the micelle, and wherein said non-ionically charged polymeric segment is hydrophilic; and
b) at least one bioactive agent.
2. The micelle of claim 1 , wherein said bioactive agent is a therapeutic agent or a chemotherapeutic agent.
3. The micelle of claim 1 , wherein said non-ionically charged polymeric segment comprises polyethylene oxide.
4. The micelle of claim 1 , wherein said ionically charged polymeric segment is a polyamino acid.
5. The micelle of claim 4 , wherein said polyamino acid is polyglutamic acid.
6. The micelle of claim 5 , wherein said hydrophobic moiety is selected from the group consisting of a hydrophobic small molecule, lipid, fatty acid, cholesterol, and a hydrophobic amino acid.
7. The micelle of claim 5 , wherein said hydrophobic moiety is a hydrophobic amino acid.
8. The micelle of claim 7 , wherein said hydrophobic amino acid is phenylalanine.
9. The micelle of claim 1 , wherein said hydrophobic moiety is selected from the group consisting of a hydrophobic small molecule, lipid, fatty acid, cholesterol, and a hydrophobic amino acid.
10. The micelle of claim 9 , wherein said hydrophobic amino acid is phenylalanine.
11. The micelle of claim 1 , wherein said micelle is linked to at least one targeting ligand.
12. The micelle of claim 1 , wherein said micelle comprises at least two bioactive agents.
13. The method of claim 12 , wherein at least one bioactive agent is hydrophobic and at least one bioactive agent is charged.
14. A composition comprising the micelle of claim 1 and at least one pharmaceutically acceptable carrier.
15. The micelle of claim 1 , wherein said bioactive agent is stabilized within the core by non-covalent electrostatic, hydrophobic, or nonpolar interactions.
16. The micelle of claim 1 , wherein said hydrophobic moiety has a molecular weight less than 1 kDa.
17. The micelle of claim 1 , wherein the degree of grafting of the hydrophobic moiety is at least 20%.